The chronic demyelinative myelopathy induced in mice by intracerebral inoculation of tissue culture cell-adapted DA virus will be further studied, under the light and electron microscopes, and by immunofluorescent methods. DA virus infection will be studied in organ cultures of mouse spinal cord, ganglia and peripheral nerve. Antigenic and morphologic changes in DA virus associated with changes in neurovirulence will be studied, using immunofluorescent and electron microscopic techniques. Cell-mediated immunity in patients with amyotrophic lateral sclerosis (ALS) will be studied by means of lymphocyte transformation to viral, CNS, acetylcholine receptor and muscle antigens. Cytotoxicity of sera and lymphocytes from ALS and multiple sclerosis patients will be assayed in neuroblastoma cells.